NEUROPATHOLOGY CORE PROJECT SUMMARY The goals of the Neuropathology Core (NPC) are to perform standardized postmortem neuropathological evaluation, and classification of subjects recruited by the Cleveland Alzheimer's Disease Center (CADRC), and to collect, store, and analyze fixed and frozen autopsy materials for use in future research. Drs. Cohen and Appleby, who bring expertise in the areas of molecular pathology and clinicopathologic correlation of neurodegenerative disease, will lead the NPC. To support AD research projects, the NPC will perform all tissue processing for histology and freezing, and immunohistochemical investigations of Alzheimer's disease (AD) and other neurodegenerative diseases. The NPC will also characterize archival tissue in the brain banks at participating sites, to more rapidly make available tissues for investigation. Toward these objectives, we have previously established the North Eastern Ohio Neuropathology (NEON) collaboration to integrate the research effort between neuropathologists at the NPDPSC, located at Case Western Reserve University (CWRU), and neuropathologists at University Hospitals (UH), and the Cleveland Clinic Foundation (CCF). The goal of the CADRC NPC is to obtain, characterize, and maintain neuropathologic specimens from subjects affected by AD and related dementias (ADRD). With over two decades of experience in conducting autopsies from across the country and maintaining neuropathologic tissue, the CADRC NPC will be maintained via infrastructure that has been proven through the work of the NPDPSC (Specific Aim 1). Experts in the field of neurodegeneration (Drs. Cohen and Leverenz) will characterize neuropathologic specimens according to accepted standardized criteria (Specific Aim 2). The CADRC will have access to and will help characterize a unique cohort of rapidly progressive AD (rpAD) samples obtained through the NPDPSC (Specific Aim 3). Finally, the NPC will foster the next generation of AD researchers by training and mentoring junior faculty in neuropathology and current concepts of basic neuroscience of age-related neurodegenerative diseases (Specific Aim 4). We anticipate that establishing a CADRC NPC will provide essential infrastructure to greatly facilitate and integrate independent research on ADRD that are currently active at CWRU and CCF.